Hormones and rabbit holes

Medicine is confusing right now. Ok, it is always confusing because we try to base it on science and science is always changing. There are always special areas that are currently a mess. Hormones!

I speak to a patient recently who is female, premenopausal, and is getting hormone replacement therapy for hot flushes and not sleeping well from an outside source. The person wants me to order hormone tests. I do order hormone tests but not the ones she has in mind. I test a TSH, thyroid stimulating hormone, to see if she is low or high in thyroid.

She is thinking of me testing estrogen and progesterone and other related hormone levels. The party line from gynecology MDs and DOs is that these are not useful tests because women’s hormone levels are so varible. However, there are lots of naturopaths out there and functional medicine MDs and DOs who will test levels. Why is the patient asking ME to test them? Most of those naturopaths and functional medicine providers do not take insurance and charge cash. Also, insurance may not pay for them anyhow because the party line is that they aren’t useful. Why would the cash providers check levels? One reason is CASH. Another is to prescribe “bioequivalent hormone replacement”. Sounds natural, right? Well, the natural thing was for the hormones to stop at menopause and all of the hormones are either made in a laboratory from plant pre-estrogens or from pregnant mare urine, so bioequivalent seems to imply natural but it really isn’t. Pills do not grow on trees, they are made by humans in laboratories.

However, I question party lines, and off I go down the hormone rabbit hole. The current guidelines are that female hormone replacement, after menopause, should be lowest dose possible and only for a maximum of three years because of the increased risk of breast cancer. This doesn’t address my question: does premenopausal hormone replacement count as part of those three years? I may need to ask gynecology. I don’t think it counts. A woman is postmenopausal when she has had no periods for a year. Or had her ovaries removed. Or if she’s had a hysterectomy and still has her ovaries, a yearly follicle stimulating hormone and lutienizing hormone test. Both tests rise when the ovaries stop making hormones and eggs.

Also, there is another caveat. We know that when men are on opioids, the opioids can suppress their hormones and lower testosterone. Here is a paper: https://pubmed.ncbi.nlm.nih.gov/31511863/. Half the men studied in multiple studies had low testosterone when on chronic opioid therapy. 18429 subjects (patients) in 52 studies. That is a lot. Women studied? NONE. What? Yeah, none. Why? Here is part of the answer: about a decade ago I worked with the UW Telepain group and asked the head of the UW Pain clinic a question. “If opioids lower hormones in men, do they in women too?”

His reply, “I don’t know.”

“Have you ever tested a woman?”

“No.”

“Isn’t that sort of sexist?”

“Yes.”

So here I am, rechecking a decade later, and we still don’t know if giving women chronic opioids messes up their hormone levels. It would be more complicated and difficult to check women. We might have to do individual hormone baselines or something in premenopausal ones, say, 2 weeks after menses. Remember that for most of the history of medicine, clinical drug trials were only done in men, because, well, sexism. They said women could get pregnant. Yes, but then we gave the drugs to women who could get pregnant. Also, postmenopausal women can’t get pregnant. The whole thing seems stupid to me.

There is an interesting new finding here: https://neurosciencenews.com/estrogen-t-cells-pain-28548/ . Apparently in women, estrogen and progesterone work on receptors at the base of the spine to reduce pain signals using T cells, part of the immune system. The article says this doesn’t happen in men, but they were studying mice. The male mice didn’t seem to have worse pain after estrogen and progesterone were blocked. The female mice were in more pain. But wait, estrogen and progesterone are produced in men as a by product of making testosterone. Less than women, until menopause. Then the 70 year old man has more estrogen and progesterone than his postmenopausal wife. The article says that they don’t know why the receptors are in women and female mice (um, my intuitive guess would be childbirth and micebirth, right? Men don’t do that and women giving birth to a child after the first one sometimes say, “WHY did I want to do THIS again?” I think those receptors are so that women and mice can get through more than one pregnancy.) Now I need to read the article again because maybe men and male mice don’t have the receptors, even though they do have some estrogen and progesterone. Maybe they just don’t have enough estrogen and progesterone.

Maybe we can’t figure out women’s hormone because men aren’t smart enough, heh, heh. Yes, that is sexist right back at all those historical figures who didn’t study women.

At any rate, that still doesn’t answer my two questions: does premenopausal hormone replacement count towards the three year total beyond which hormone replacement increases the risk of breast cancer? And does chronic opioid treatment lower women’s hormone levels?

_________________

For the Ragtag Daily Prompt: hormone.

I took the photograph of a Port Townsend rabbit in 2011.

My Monday is Tuesday

I am a slacker on Tuesday’s Ragtag Daily Prompt! Not really, it’s just that that is my back to work day and I am getting ready in the morning and I think, “I will do it later.” Last night I cooked a pork tenderloin with peaches, kale and green beans, but then afterwards I fell asleep by 7:30. I guess Tuesday particularly tires me out. I met the new doctor yesterday and I had two patients who took nearly an hour each.

I found another farm stand this weekend and bought tons of vegetables and some fruit. I am still trying to do half vegetables at each meal. It takes time. I bought more pattypan squash to roast, it turns sweet and delicious. Quick, while the summer squash is available!

I also took four books to the library and took out eight more. I switched cookbooks because I did not like the one I had. This one looks much better. And a smattering of nonfiction, science fiction and fiction and silly romances or fantasy romance for when my brain is tired. I avoid the horror aisle, there’s enough of that in the news.

Shelves with many library books

For the Ragtag Daily Prompt: science fiction.

Covid 19 and the heart

This is from the University of New Mexico Roam Echo PASC (Post Acute Sequelae of Covid-19) talk on 11/9/2023 over Zoom.

Cardiovascular Outcomes in Post-COVID Conditions
Jeffrey Hsu, MD, PhD, FACC, Assistant Professor, Division of Cardiology – University of California, Los Angeles Health and Founder, COVID Cardiology Program – University of California, Los Angeles 

I am going to include the references in the order that Dr. Hsu talked about them. This is a sobering and upsetting lecture with the research showing a post Covid-19 increase in cardiovascular risk factors (cholesterol, hypertension, diabetes), and an increase in cardiovascular events in people with no previous cardiovascular diagnosis including heart attack, stroke, pulmonary embolus, blood clots and sudden death.

I don’t expect the general population to read the studies, but look at a few of them. It is very very impressive, the amount of work being done. Now let’s explore the talk and boil it down to three sentences for primary care to explain in clinic. Right. (You can always skip to the last two paragraphs if you get overwhelmed, and come back later.)

Part 1: The Research.

The first paper is about veterans without cardiovascular disease, followed for one year after Covid-19, matched with a cohort who did not have Covid-19. This is before immunization was available. They were studying the heart and cardiovascular risk. The veterans who had had Covid-19 infection were twice as likely to be diagnosed with cardiovascular risk then the veterans who had not had Covid-19. The risk was higher in the veterans with more severe Covid-19, the risk was present in all subgroups: old, young, male, female, with or without other risk factors. At two years out, the people who had been hospitalized for Covid-19 still had a persistent increased risk of death and cardiovascular incidents (heart attack, stroke, sudden death, blood clots).

To be clear, this is NOT Long Covid patients. This is just a cohort of veterans who had Covid-19. This would indicate that everyone who had Covid-19 has an increased cardiovascular risk.

Here is the first paper: 1. https://www.nature.com/articles/s41591-022-01689-3

Two more papers looked at more general populations who got Covid-19 before the vaccine was available and found the same thing. The veterans tended to be older and more male patients, but the general population studies found the same pattern in women and younger patients. Papers:

2. https://www.scientificamerican.com/article/the-risk-of-heart-disease-after-covid/, “Health modeller Sarah Wulf Hanson at the University of Washington’s Institute for Health Metrics and Evaluation in Seattle used Al-Aly’s data to estimate how many heart attacks and strokes COVID-19 has been associated with. Her unpublished work suggests that, in 2020, complications after COVID-19 caused 12,000 extra strokes and 44,000 extra heart attacks in the United States, numbers that jumped up to 18,000 strokes and 66,000 heart attacks in 2021. This means that COVID-19 could have increased the rates of heart attack by about 8% and of stroke by about 2%. “It is sobering,” Wulf Hanson says.

3.https://www.nature.com/articles/s41591-023-02521-2

Non hospitalized patients had decreased risk for some cardiovascular problems but not all and still had significantly higher risk than people who had not had Covid-19. I am busily thinking UH-OH, this is really bad, in this lecture.

He stated that the data is not in yet about vaccination, whether it lowers the cardiovascular damage compared to unvaccinated.

The initial study was on veterans, mostly male and mostly white, but then was replicated in other similar studies that were not on veterans, but on a general population.

From the second and third study, 700,000 patients with a mean age 40 and more than half female, were studied for new cardiovascular disease in the year following Covid-19 and found an increased risk of death within one year, 0.34% vs 0.28% HR 1.6. That was in 2020, a nonvaccinated population. Another study showed similar results, 13,000 patients with Covid-19 and 26,000 without, average age 51. There was a similar risk increase in cardiovascular disease and an increased risk of death within one year.

4. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00349-2/fulltext

5. https://jamanetwork.com/journals/jama-health-forum/fullarticle/2802095

So do other infections do the same thing? Studies of acute risk of myocardial infarction risk after influenza, done before the pandemic, indicate an increased risk of myocardial infarction within one week after infection, but not beyond that week. So Covid-19 is really really nasty to our cardiovascular system.

6. https://www.nejm.org/doi/10.1056/NEJMoa1702090

7. https://www.nejm.org/doi/10.1056/NEJMra1808137

Pneumonia and sepsis can increase risk of cardiovascular disease, but there have not been the extensive studies as in Covid-19. More and better studies.

One to two years after diagnosis, there is increased cardiovascular and cerebrovascular risk, both:

  1. Cardiovascular risk factors, worsening after covid
  2. Thrombosis risk

8. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(22)00044-4/fulltext

The risk of is up diabetes 40% in the post Covid-19 patients. That does not mean that 40% are diagnosed with diabetes, but that the risk is higher after Covid-19. For example, if in the non-Covid cohort 100 of 1000 40 year olds develop type 2 diabetes, then it’s 140 of 1000 in the post Covid-19 group.

The risk of dyslipidemia in 50,000 patients went up 24%. Dyslipidemia means increased LDL cholesterol or increased triglycerides and lower HDL or all of them.

9. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(22)00355-2/fulltext

10. https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.123.21174

Hypertension is up too and weight gain.

11. https://www.nature.com/articles/s41577-022-00762-9

New onset hypertension is up 22% in hospitalized patients post Covid-19 and 11% in unhospitalized post Covid patients.

Myocardial infarction (heart attack) and ischemic stroke both go up. Ischemic stroke is the more common kind of stroke and is the clotting version. Bleeding strokes are less common.

Why does Covid-19 do this? What is the mechanism? The studies are pointing towards thromboembolism as the mechanism in both increased cardiovascular risk factors (dyslipidemia, hypertension, stroke, heart attack, clots). Thrombosis means clots. Remember the talk about micro-clots? (My write up here: https://drkottaway.com/2023/04/14/xeno-or-infection-phobic/). Micro-clots can lead to bigger clots. A clot in a heart artery causes a heart attack; in the brain an ischemic stroke; a clot in the leg can break into pieces and block the lung arteries. Irritation in the heart and the arteries can increase blood pressure. I’m not sure how it can increase diabetes, but it does.

Next he shows a slide about thrombosis and how complex it is. Sars covid-19 seems to promote perfect storm of events that leads to environment for thrombosis in multiple ways.

Covid-19 infects epithelial cells, causes a hyperactive immune response, orchestrates subsequent response, causes platelet hyperactivation and then hyperactive innate immune response, causes damage to glycocalyx that protects and vascular endothelial injury, decreases antithrombogenic and increases prothrombogenic activity which promotes thrombosis in the vasculature, platelet activation and coagulopathy. Got that? No? Me either, my last immune system class was in 1988 when I was working at the National Institutes of Health. It’s bad, meaning it can kill us or cause damage that is disabling.

12. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30937-5/fulltext

My notes are a bit disjointed here: The endothelial cells (which line arteries) express H2 receptors that Covid-19 virus needs to enter the cells. The H2 receptors are also in glomerular capillary loops (kidneys), and immune cells and cause apoptosis of lung endothelial cells. Apoptosis is a form of programmed cell death that occurs in multicellular organisms and some eukaryotic microorganisms. So you don’t want your lung cells doing that. Lung, small bowel, and pulmonary microvasculature can all be affected.

13. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(22)00355-2/fulltext

Plaque in human coronary vessels, in the immune cells, spike and Sars cov 2 identified in coronary artherosclerotic plaque.

Direct on coronary and cerebrovascular cells. (Ok, I don’t know what I meant by this note.)

Part II: Now what? What is our approach to healing this?

There is still limited data! (The clinical trials are roaring along but they take time.) Here are a bunch of studies, all using blood thinners. Blood thinners include aspirin, plavix, heparin, enoxaparin or apixaban. Do NOT start aspirin at home at this point, because when you add a blood thinner, there is a risk of bleeding, including bleeding stroke and intestinal bleeding. So far, the studies are discouraging.

Aspirin 150Mg Recovery trial: no difference in mortality: major bleeding 1.6% vs 1/0 % Lancet 2022. This is a double baby aspirin dose, 30 days in study, no benefit in acute setting.

14. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30937-5/fulltext

Non critically ill hosp patients ACTIV 4A trial P2Y12 inhibitor – heparin alone or clopidigril (plavix) plus heparin, no benefit, major bleeding 2.0% vs 0.7% so worse in the both group.

15. https://www.nejm.org/doi/10.1056/NEJMoa2103417

16. https://doi.org/10.1001/jama.2021.17272

Harmed patients with severe disease.

ACTIV-4B aspirin or apixiban in outpatient, stopped early, event rate low, higher rates of minor bleeding in the 5mg apixiban group.

Feedom covid 19 trial: Non ICU Hospitalized, compared prophylactic heparin to enoxaparin or apixaban. Signal to provide benefit, lower rates of death and intubation, similar bleeding rates

17. https://www.sciencedirect.com/science/article/pii/S0735109723045278?via%3Dihub

So what does our Post Covid Cardiologist recommend to physicians and patients:

First year post covid: look for cardiovascular symptoms.

Screen for risk factors, hypertension, diabetes, hyperlipidemia, obeisity.

Optimization of risk factors, smoking cessation (and I would add that alcohol also causes damage to the heart and arteries, though tobacco is worse.

Assess candidacy for statin therapy for primary prevention.

18. https://cardiab.biomedcentral.com/articles/10.1186/s12933-021-01359-7

There is a study of triple therapy (meaning THREE blood thinners) that showed improvement but that was in older patients who already have heart disease before Covid-19. So it doesn’t apply.

He says there aren’t any good studies of blood thinners in Long Covid-19 yet and it is not clear that the Long Covid people are worse as far as the cardiovascular risk than everyone else. And remember, these studies are on unvaccinated people, so for the year following the first year of Covid-19. We don’t have the results for vaccinated people. He says that if someone is high risk or has cardiac symptoms chest pain etc put on 81 mg aspirin and a statin (and work it up, of course. Do the testing.

For now use anticoagulation (blood thinners) only if there is clear evidence of thrombus: deep venous thrombosis or pulmonary embolus. Freedom covid-19 study showed major bleed risk 0.1-0.4%.

The cardiologist speaker has not started triple therapy on any patents given unknown benefit at this time, with known significant major bleeding risk. He recommends shared decision making, meaning the patient should be presented with the risks and choices. Um, ok, boil this talk down into three sentences. Good luck. EEEEEEE!

Part III: Summary.

Whether you had Covid-19 before being vaccinated or after, or aren’t sure if you ever had it, it is worth seeing your provider to check your blood pressure, do diabetes screening, stop smoking (anything, and I include vaping in that), reduce or eliminate alcohol, keep your weight reasonable, check your cholesterol and go to your provider if there is any weirdness post Covid-19. And if you have not been vaccinated, oh, my gosh. Unless you have an immunology problem where your immunologist says “NO!”, get vaccinated.

Lastly, I’ve heard many claims that death rates were “over reported” for Covid-19. No. In a death certificate, the acute injury or infection is reported FIRST and then other related causes. Such as: Covid-19, ischemic stroke, hypertension, tobacco overuse syndrome. There were MORE strokes and heart attacks and sudden death, with Covid-19 as the final straw in many people who already had cardiovascular disease. They died sooner than they would have if not infected. That is not over reporting.

____________________________________________________________________________

A friend, Brent Butler, took the photograph, used with permission. I think it shows how I felt after this talk. Yet I still have hope, because you can’t deal with something unless you know about it.

If you want a link for the talks, message me. Anyone can tune in.

Covid-19 continues to fandangle us. There. I verbed the Ragtag Daily Prompt: fandangle.

BRAINS

On Thursday and Friday I spent six hours daily glued to zoom, for the Inflammatory Brain Disorders Conference. Speakers, both physicians and scientists and physician-scientists, from all over the world, spoke. The research is intensive and ongoing. They spoke about Long Covid, both the immune response and “brain fog”. They spoke about anti-NMDA antibody disorder (the book Brain on Fire) and now there have been over 500 people identified with that disorder and a whole bunch more antibody-to-brain disorders! They talked about PANS and PANDAS and chronic fatigue and Mast Cell Activation Disorder and about the immune system over and over. The new information is amazing and I need to reread all my notes. Psychiatry and Neurology and Immunology are all overlapping in research, along with Rheumatology, since these disorders overlap all four.

It is a medical revolution in the making.

Best news was that 96% of Long Covid patients are better by 2 years from getting sick. That is tremendously reassuring, though the number may change. And the definition of Long Covid is still being sorted out and we do not know if people relapse.

I felt that MY brain was MELTED by the end, but I managed to enjoy the Rhododendron Parade on Saturday and just puttered around the house on Sunday.

366

Today I have posted for 366 days in a row, so I am past the one year point. That pleases me. Why do numbers and years and that sort of mark please us so much? I think it is because we do have to pay attention to seasons and when things grow and where food is and what to wear… All of it.

Happy New Year!

The photograph is from one of our local festivals. I will let you figure out which one.

Dinosaur dreams

Dinosaur Dreams

The problem
With Intelligent Design
Is those old bones
Those dinosaurs

Also that of 10,000 dreams of creation
One would be right
And the followers of all the others
Consigned to hell
If so, I go gladly, clutching
Dinosaur bones to my chest
And will enjoy the diversity
Not the narrow heaven with a narrow
Small-minded deity

But is evolution right?

Well, I think it’s on the right track

But wholly done and all correct?

After all, think how often
Medicine has been wrong
Think of tobacco and vioxx
Think of Galen, over 2000 years ago
Thinking that evil humors built up in the uterus
Causing hysteria
External pelvic massage was the cure
For over 2000 years
For old maids, widows and nuns
Who had no male to cleave unto
Massage was a treatment into the early 1900s
And now we wonder about prozac too

Evolution is an evolving science

I think of when my son was four
And he watched “Jurassic Park”
Against my wishes
Because I thought it was too violent
He studied it carefully many times

One day he asked me, anxiously,
“Mom, is DNA real?”
To check that it wasn’t another of those Santa stories
I was able to reassure him
Yes, I think DNA is real
He was pleased

A few days later he announced
That when he grows up
He wants to be a plant and animal scientist
Extract DNA from amber
And grow those dinosaurs

A laudable ambition
For any four year old

If God left the dinosaur bones
Around to fool us
And they never lived
She has a nasty sense of humor
And my son and I will not forgive

I believe in evolution
And dream of dinosaurs

written in 2009